Endocrine Abstracts

Biological therapies include interleukins, interferons, and MABs. Over the past few years, the use of MAB to treat cancer and other diseases such as multiple sclerosis (MS) have increased; some of these frequently cause endocrine side effects.

Alemtuzumab, a MAB directed at CD52 on T and B lymphocytes, is very effective in reducing relapse rates and improving disability in relapsing remitting MS, however is frequently (16–35%) associated with the onset of thyroid disease, most commonly Graves’ disease (GD), which can occur many years after it’s use. Family history of thyroid disease and smoking are risk factors. A subset of affected patients follow a fluctuating course, which can mean control of disease is difficult. Eye disease seems less common than in non-Alemtuzumab induced GD, however it is not entirely clear whether these patients run a more indolent course and experience similar relapse rates.

Agents that modulate immune checkpoint proteins such as CTLA4 and programmed death 1 (PD1) have been shown recently to be effective in advanced melanoma, NSCLC and other cancers. The anti-CTLA4 MAB ipilimumab results in hypophysitis in up to 17% of patients, with a predilection to TSH and ACTH deficiency. Many patients have diffuse pituitary enlargement on MRI. Recovery is variable, with the hypothalamus–pituitary–gonadal axis recovering most frequently (57%), but the hypothalamus–pituitary–adrenal axis only recovering in 1–2%. High dose steroids are often given but may not significantly alter the course. The PD1 inhibitors Nivolumab and Pembrolizumab are frequently associated with thyroid dysfunction (hypothyroidism in up to 10%, hyperthyroidism up to 6.5%). Thyroiditis has also been described but the frequency is not yet known.

Given their efficacy, it is likely that we will encounter these agents and their side effects more frequently in clinical practice, however the optimal surveillance and management strategy is not yet clear.